Irritable bowel syndrome (IBS) is a multifactorial disorder marked by recurrent abdominal pain or discomfort and altered bowel function. It affects between 10 and 20 percent of people in the developed world, about one-third of whom have IBS associated with diarrhea (IBS-D). IBS-D is commonly treated with loperamide, an opioid antidiarrheal agent with no analgesic properties, which inhibits the release of acetylcholine and prostaglandins in the gut, thereby reducing peristalsis and slowing intestinal transit time, which also favorably affects water and electrolyte movement through the bowel. Serotonin (5-HT) also plays an important role in the regulation of GI motility and the activation of 5-HT3 receptors. Alosetron, a 5-HT3 receptor inhibitor, has been used to treat abdominal pain and discomfort associated with IBS. Blockade of 5-HT3 receptors on cholinergic nerve endings also inhibits colonic motility, which can be beneficial for the treatment of IBS-D. However, alosetron is associated with potentially life-threatening ischemic colitis, and its use is limited to women with severe, chronic IBS-D who have failed to respond to conventional treatment.
Clearly, there is a need in the art for alternative treatments for IBS and other inflammatory diseases of the gastrointestinal (GI) tract, including medicaments that reduce associated pain and discomfort and inhibit GI motility.